TNF-α - mediated peripheral and central inflammation are associated with increased incidence of PND in acute postoperative pain

Abstract

Abstract Background Acute postoperative pain plays an important role in the perioperative neurocognitive disorders (PND). The pathogenesis of PND is still unknown, but it is generally believed that peripheral and central nervous system inflammation play an important role, and acute postoperative pain is also thought to aggravate postoperative inflammatory response. The aim of the present study is to explore the effect of acute postoperative pain on peripheral and central nervous system inflammation and related cognitive impairment behaviour in elderly rats after surgery. Methods Rats were assigned into four groups: control, surgery for internal fixation for tibial fracture, surgery with analgesia using intraperitoneal morphine, and morphine without surgery. Pain was assessed by the Subjective Pain Scale. The spatial memory of rats was assessed by the Morris water maze (delayed matching task) from the second day to the seventh day after surgery (POD2-POD7). In part of the rats, the pro-inflammatory cytokines TNF-α in plasma, the medial prefrontal cortex (mPFC), and the hippocampus were determined by ELISA on the POD2. The activation of microglia and the expression of c-Fos in the hippocampal CA1 regions and mPFC were detected by the immunohistochemical method on the POD2. Results Acute postoperative pain and spatial memory impairment occurred after operation, and postoperative analgesia could significantly improve the both parameters. Additionally, on the POD2, the levels of TNF-α in plasma, hippocampus and mPFC were significantly increased, while the activation of microglia cells and the expression c-Fos in the hippocampal CA1 regions and mPFC were significantly increased. And postoperative analgesia with morphine significantly inhibited the above reactions. Conclusion Our data suggest that acute postoperative pain increases the incidence of perioperative neurocognitive disorders. Peripheral and central nervous system inflammation may be involved in this cognitive impairment. And reducing the intensity of acute postoperative pain may be one of the main preventive strategies for PND.

Keywords

• Perioperative neurocognitive disorders (PND)
• Acute postoperative pain
• TNF-α
• Microglia
• C-Fos